New findings from a large phase I study of 411 patients with advanced melanoma show that the PD-1 targeting antibody MK-3475 yields long-term responses in a high percentage of patients. These results were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

In the study, the 1-year overall survival was 69% across all patient subgroups, and responses were ongoing in 88% of patients at analysis, after a median follow-up of 12 months. Responses occurred across all dose regimens and in various subgroups of patients, including patients whose disease progressed following ipilimumab therapy, for whom there are currently no effective treatment options.

“This is probably the biggest phase I trial ever conducted in oncology. We were excited to see that MK-3475 was effective in previously untreated patients as well as in those who had multiple prior therapies, including ipilimumab,” said lead study author Antoni Ribas, MD, PhD, a professor of medicine at the David Geffen School of Medicine at the University of California in Los Angeles. “These are early data, but they tell us we are on to something really important.”

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The study enrolled 221 patients with prior ipilimumab treatment and 190 patients who had not previously received ipilimumab. All patients had advanced melanoma that had spread to the skin, lungs, or other major organs. Three different MK-3475 dose schedules as a single agent were tested.

“Importantly, MK-3475 is effective regardless of prior ipilimumab treatment. Anti PD-1 as a single agent is a major breakthrough and improves on the initial success of ipilimumab in metastatic melanoma,” said Steven O’Day, MD, ASCO Expert.

Overall, 34% of patients experienced tumor response, as assessed by Independent Review, including 40% of patients not previously treated with ipilimumab and 28% of patients whose disease progressed on prior ipilimumab. Responses were durable with 88% ongoing at the time of analysis. Activity was observed across all dose levels and patient subgroups, irrespective of prior ipilimumab therapy, performance status, LDH levels, BRAF mutation status, tumor stage, and number and type of prior therapies.

The estimated 1-year survival rate was 69%, and median overall survival duration was not reached. The estimated 1-year survival rate was 74% in patients not previously treated with ipilimumab and 65% in patients who received prior ipilimumab therapy.

Overall, 8% of patients experienced serious treatment-related side effects, but only 4% discontinued treatment due to a drug-related side effect.

The FDA had previously granted a breakthrough therapy designation to MK-3475 for unresectable or metastatic melanoma. In May 2014, the FDA granted MK-3475 a priority review designation under its Accelerated Approval program. Ongoing randomized controlled studies are assessing the efficacy and safety of MK-3475 in advanced melanoma patients not previously treated with ipilimumab and those who progressed on or after ipilimumab. Studies in an adjuvant setting are planned.

An expanded access program for MK-3475 is now available for eligible patients with advanced melanoma who have been previously treated with ipilimumab and, if indicated, a BRAF inhibitor.

This research was supported by Merck.